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Prognostic cytogenetic markers in childhood acute lymphoblastic leukemia
A Settin1, M Al Haggar, T Al Dosoky
1Genetic Unit, Mansoura University Children's Hospital, Mansoura, Egypt.
Insights
Cytogenetic analysis in childhood acute lymphoblastic leukemia (ALL) can identify specific chromosomal aberrations linked to chemotherapy resistance. These findings aid in predicting treatment outcomes and personalizing therapy for pediatric ALL patients.
Area of Science:
- Pediatric Oncology
- Hematology
- Genetics
Background:
- Childhood acute lymphoblastic leukemia (ALL) presents a significant challenge, particularly in cases resistant to initial chemotherapy.
- Identifying prognostic markers is crucial for optimizing treatment strategies and improving patient outcomes.
Purpose of the Study:
- To investigate the role of conventional and advanced cytogenetic analysis in children with acute lymphoblastic leukemia (ALL) who exhibit resistance to induction chemotherapy.
- To correlate specific cytogenetic abnormalities with treatment response and resistance in pediatric ALL.
Main Methods:
- The study involved 63 children diagnosed with ALL, categorized by their response to induction chemotherapy (remission vs. failure).
- Methods included clinical examination, complete blood count (CBC), bone marrow (BM) examination, karyotyping, fluorescence in situ hybridization (FISH) for translocations, and flow cytometry for immunophenotyping and minimal residual disease detection.
Main Results:
- While some factors like white blood cell count and immunophenotype (L2) showed trends towards better remission, they were not statistically significant.
- Analysis of 40 informative karyotypes revealed varying ploidy patterns, with the most frequent showing better remission rates.
- Specific chromosomal aberrations, including deletions (2p, 3q, 10p, 12q), translocations (chromosome 5), trisomies (16, 21), monosomies (5, X), and inversions (5, 11), were associated with chemotherapy resistance.
Conclusions:
- Cytogenetic and molecular characterizations provide valuable prognostic criteria for childhood ALL.
- These findings can guide proper therapy allocation, leading to more personalized treatment approaches for pediatric ALL patients.
Objective:
To evaluate children with acute lymphoblastic leukemia (ALL) showing resistance to immediate induction chemotherapy in relation to conventional and advanced cytogenetic analysis.
Methods:
This work was conducted on 63 ALL children (40 males and 23 females) with age range 4.5 months-16 years (mean = 7.76 years). They included 37 cases attained true remission and 26 complicated by failure of remission, early relapse or death. They were subjected to history, clinical examination and investigations including CBC, BM examination, karyotyping, FISH for translocations and flowcytometry for immunophenotyping and minimal residual disease diagnosis.
Results:
Cases aged 50.000/mm3 also showed better but non-significant remission rates. Most of the present cases were L2 with better remission compared to other immunophenotypes. Forty informative karyotypes were subdivided into 15 hypodiploid, 10 pseudodiploid, 8 normal diploid and 7 hyperdiploid cases; the best remission rates were noticed among the most frequent ploidy patterns. Chromosomes 9, 11 and 22 were the most frequently involved by structural aberrations followed by chromosomes 5, 12 and 17. Resistance was noted with aberrations not encountered among remission group; deletions involving chromosomes 2p, 3q, 10p and 12q; translocations involving chromosome 5; trisomies of chromosomes 16 and 21; monosomies of 5 and X and inversions of 5 and 11.
Conclusion:
Some cytogenetic and molecular characterizations of childhood ALL could add prognostic criteria for proper therapy allocation.
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